This application asks for support of our ongoing research in the inter-relationships between vasodepressor prostaglandins, renin-aldosterone, renal function, and vascular reactivity in man. Recent work in our laboratory has lead to a validated and accurate PGE immunoassay useful in human urine and blood. We have recently in a series of studies shown that renal PG's are important in renin release in normal man which extends the parallel reports from studies in animal models. We propose three areas of research in the new grant period. First, we wish to explore prostaglandin production and origin in subjects with chronic liver disease. In preliminary studies we find that ascites patients have 10-fold increase in PGE, that prostaglandin inhibitors reduce renin (PRA) and aldosterone, reverse angiotensin pressor resistance and markedly impair renal function (PAH and Creatining Clearance). These studies suggest that as in Bartter's Syndrome, renal prostaglandins play a supportive role in various renal disorders of electrolyte balance and high renin states. Non-platelet blood PGE may arise normally from the kidney, but in very preliminary studies of cirrhotics, the abnormal production of PGE may arise largely from the GI tract. Urinary PGE is said to arise solely from the kidney, however, no steady state or quantitative data is available. This approach will probably be widely used and we propose to quantitatively determine whether any significant labeled PGE2 given arterially appears in the urine. Constant infusion of PGE1 and PGE2 will allow determination of renal extraction, the transfer constant from blood to urine and overall renal clearance of PGE. Comparison of specific activities of PGE entering and PGE excreted in urine will determine intra-renal total production which can be compared with renal excretion mass. Finally, two small but interesting protocols are proposed in the area of human renal sodium handling and PGE. The first will probe the role of prostaglandin and bradykinin during mineralocorticoid escape and the second ascertain whether natiuresis from an acute saline load alters urine PGE and is blunted by PG inhibition.